VRC-HIVMAB060-00-AB (VRC01) in People With Chronic HIV Infection Undergoing Analytical Treatment Interruption

Recent advances in antibody cloning technologies have led to the discovery of a number of
highly potent, HIV-specific, broadly neutralizing monoclonal antibodies from B cells of
HIV-infected individuals. It has been shown that certain broadly neutralizing HIV-specific
antibodies can prevent acquisition of the virus, suppress viral replication, delay and/or
prevent plasma viral rebound following treatment interruption in Simian Immunodeficiency
virus (SIV)-infected animals and block cell-to-cell transmission of laboratory-adapted HIV in
vitro. However, it is unclear what in vivo effects these antibodies might have on plasma
viral rebound in HIV-infected individuals following discontinuation of combination
antiretroviral therapy (cART).

In this regard, it has been shown that virtually all infected individuals who initiated cART
during the chronic phase of infection experience plasma viral rebound upon cessation of
therapy. Current research on the treatment of HIV-infected individuals has been heavily
focused on developing strategies aimed at achieving sustained virologic remission in the
absence of cART. Thus, it is of great interest to investigate whether a potent HIV-specific
monoclonal antibody, such as VRC01, can prevent plasma viral rebound in infected individuals
upon discontinuation of cART. We propose to examine the effect of VRC01 on plasma viral
rebound in HIV-infected individuals following analytical treatment interruption (ATI).

- INCLUSION CRITERIA

1. Age 18-65 years old.

2. HIV-1 infection and clinically stable.

3. In general good health and with an identified primary health care provider for
medical management of HIV infection and willing to maintain a relationship with a
primary health care provider for medical management of HIV infection while
participating in the study.

4. CD4+ cell count >450 cells/mm^3 at screening.

5. Documentation of continuous cART treatment with suppression of plasma viral level
below the limit of detection for greater than or equal to 3 years. Subjects with
blips (i.e., detectable viral levels on cART) prior to screening may be included
provided they satisfy the following criteria:

1. The blips are <400 copies/mL, and

2. Succeeding viral levels return to levels below the limit of detection on
subsequent testing.

6. Willingness to undergo ATI.

7. Laboratory values within pre-defined limits at screening:

1. Absolute neutrophil count >1,000/mm^3.

2. Hemoglobin levels >10.0 g/dL for men and >9.0 g/dL for women.

3. Platelet count >100,000/mm^3.

4. Prothrombin time (PT) and partial thromboplastin time (PTT) <1.5 upper limit
of normal (ULN).

5. Estimated or a measured creatinine clearance rate of greater than or equal
to 50 mL/min as determined by the NIH Clinical Center laboratory.

6. AST and ALT levels of <2.5 x ULN.

8. Willingness to have samples stored for future research.

Reproductive Risks

Contraception: The effects of VRC01 on the developing human fetus are unknown. For this
reason, men and women of childbearing potential must agree to use adequate pregnancy
prevention per the investigator. This includes highly reliable established lifestyle of
complete abstinence of potentially reproductive sexual activity, or use of BOTH a long term
hormonal or barrier (e.g. implant, depot injection, IUD in female participant or female
partner of participant) method of contraception that is fully effective prior to dosing,
COMBINED WITH a barrier method (male or female condom) for all potentially reproductive
sexual activity. Pregnancy prevention must be maintained as effective and practiced
continuously for the duration of study participation. Females of childbearing-age must have
a negative pregnancy test result prior to receiving VRC01. During the course of the study,
if a female participant, or the partner of a male participant suspects or in fact becomes
pregnant, the effected participant should inform the study staff immediately, as well as
the woman's primary care physician. Subjects must use safe sex practices during the trial,
and particularly during the ATI phase, when risk of transmission of HIV may be increased.

- EXCLUSION CRITERIA

1. Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface
antigen (HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a
positive test for HCV RNA. Subjects with a positive test for HCV antibody and a
negative test for HCV RNA are eligible.

2. Documented virologic failure to >1 cART regimen.

3. HIV immunotherapy or vaccine(s) received within 1 year prior to screening.

4. Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza,
pneumococcal polysaccharide) received within 2 weeks prior to study enrollment.

5. Receipt of other investigational study agent within 28 days of enrollment.

6. Any active malignancy that may require systemic chemotherapy or radiation
therapy.

7. Systemic immunosuppressive medications received within 3 months prior to
enrollment (Not excluded: corticosteroid nasal spray or inhaler; topical
corticosteroids for mild, uncomplicated dermatitis; or oral/parenteral
corticosteroids administered for non-chronic conditions not expected to recur
[length of therapy less than or equal to 10 days, with completion in greater than
or equal to 30 days prior to enrollment]).

8. History or other clinical evidence of:

1. Significant or unstable cardiac disease (e.g., angina, congestive heart
failure, recent myocardial infarction).

2. Severe illness, malignancy, immunodeficiency other than HIV, or any other
condition that, in the opinion of the investigator, would make the subject
unsuitable for the study.

9. Active drug or alcohol use or any other pattern of behavior that, in the opinion
of the investigator, would interfere with adherence to study requirements.

10. Breast-feeding.